Cellular response to pulsatile molecular signals, rather than steady-state signals, may be nearly universal and, if demonstrated, will be a discovery of fundamental importance. The aim of this research is to construct and test a unique cell micro-perifusion system capable of making dynamic measurements on-line to identify what pulsatile signal characteristics (compounds, pulse height (concentration), pulse width, order and timing) evoke cellular response. KMS Fusion will develop the perifusion system and biological experiments will be performed at the Program for the Study of Reproduction and Differentiation of The University of Michigan. We expect to establish the feasibility and importance of using dynamic, on-line, perifusion systems for the stimulation and analysis of cells and tissues in vitro. A family of marketable instruments should evolve, providing powerful, flexible ways to monitor the dynamics of living cells in response to a variety of drug regimens, toxins, environmental or other samples. Such instruments might be indispensable to pharmaceutical houses, industrial firms needing process control of biological processes and of use in medical diagnosis.